Demographic, clinical, and surgical features of patients undergoing thyroidectomy due to thyroid lesions in Southern Iran: A cross‐sectional study

Abstract Background and Aims The incidence of thyroid cancer has witnessed a significant global increase and stands as one of the most prevalent cancers in Iran. This surge is primarily attributed to the escalating incidence of papillary thyroid cancer (PTC), with overdiagnosis emerging as an equally noteworthy factor. Consequently, this study aims to ascertain the incidence of thyroid cancer, along with its clinical presentation, demographic characteristics, and surgical features in patients undergoing thyroid surgery. Methods This cross‐sectional study involved the evaluation of patient files from referral centers in Shiraz spanning the years 2015−2020. Demographic and clinical information pertaining to thyroid cancer was extracted and subsequently analyzed using SPSS software. Results A total of 533 documented cases of thyroid cancer undergoing surgery revealed an annual rate of 89 cases in our location. The average age of the patients was 43.9 ± 13.4 years (ranging from 13 to 92), with females constituting 429 (83.5%) of the cases, and 278 (54.1%) being malignant. Conventional PTC emerged as the most prevalent pathology, accounting for 239 (45.0%) of the cases. Patients with thyromegaly exhibited significantly higher incidences of nonmalignant tumors (p = 0.01), while those with malignant tumors were notably younger than those with nonmalignant tumors (p = 0.001). Conclusion Our study revealed a progressive rise in the number of patients undergoing thyroidectomy over the years, with PTC constituting the majority of cases. Malignant cases were more frequently observed in younger patients, and in smaller lesion sizes, highlighting the importance of early screening and optimizing detection methods, especially in high‐risk populations.

There has been a significant rise in the number of individuals diagnosed with thyroid cancer over the last 30 years in the United States and other developed countries. 1,28][9] The majority of thyroid cancers, such as papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), poorly differentiated thyroid cancer, and anaplastic thyroid cancer (ATC), originate from follicular thyroid cells.[12][13][14] Over 90% of thyroid nodules are benign lesions that will never become clinically significant. 15However, in some cases, whether palpable or non-palpable, they have the potential to be malignant. 16e 2015 ATA guidelines recommend total thyroidectomy in low-to intermediate-risk patients. 17As per the guidelines defined boundaries for central lymph node dissection (CLND), level VII station lymph nodes (LN) should be included in CLND.8][19] A comprehensive history and physical examination, laboratory techniques, neck US, and at times FNA are essential for distinguishing lesions with a low likelihood of malignancy from those that are malignant.
In Iran, thyroid cancer is the seventh most common cancer in females and the 11th most common cancer in males, in which its incidence varies among different provinces. 20,21Fars province reported more than 10 incidences of thyroid cancer per 100,000 in 2010, which, compared to 1990-2001, demonstrates a noticeable increase from 0 to 1 per 100,000. 22Given the high volume of patients undergoing thyroidectomy at our referral center, we designed this retrospective study to evaluate the incidence, demographic characteristics, clinical presentation, and surgical features of patients undergoing thyroidectomy due to thyroid lesions.
Our objective also includes reporting the prevalence of various thyroid pathologies in our study location and assessing the association between the patients' features and their pathology reports to identify potential risk groups for thyroid malignancies.

| RESULTS
During the study period, a total of 533 thyroid cancer cases that underwent surgery were documented, indicating an average annual rate of 88.8 cases.Among these patients, 19 were excluded due to an incomplete final pathology report.The remaining 514 cases were included in our analysis.The average age of the patients was 43.9 ± 13.4 years, ranging from 13 to 92, with 429 (83.5%) of them being females.In our study, 278 cases (54.1%) were identified as malignant, while 236 cases (45.9%) were nonmalignant.Table 1 illustrates the baseline features of the patients in our study.The analysis revealed that gender and a previous history of subtotal thyroidectomy showed no significant association with thyroid malignancy.However, patients with thyromegaly exhibited significantly higher incidences of nonmalignant tumors (p = 0.01).Additionally, patients with malignant tumors were significantly younger compared to those with nonmalignant tumors (p = 0.001).
Table 2 illustrates the clinical and surgical features of the patients and their association with tumor malignancy.Total thyroidectomy (92.1%, p < 0.001) and CLND (29.8%, p = 0.005) were the most frequently performed surgical methods in our study, and both were significantly associated with tumor malignancy.Among the majority of the patients, no nodules were involved (58.9%), and an involved/ resected LN ratio of 97.04% (197/203) was observed.The average size of the largest tumor diameter was 2.1 ± 1.78 cm, ranging from 0.1 to 14 cm.Malignant pathologies more frequently underwent total thyroidectomy (p < 0.001; OR: 3.86; 95% CI: 1.78−8.40),while subtotal thyroidectomy was more frequently carried out in nonmalignant pathologies (p = 0.001; OR: 4.51; 95% CI: 1.65-12.34).Malignant tumors were significantly smaller in size, area, and volume compared to nonmalignant tumors.Lesions measuring ≤1 cm in largest diameter were strongly correlated with malignant histopathology (90.4%), while lesions with a largest diameter of above 5 cm were mostly seen in nonmalignant cases (61.1%).The majority of malignant lesions were located unilaterally (51.79%; p < 0.001).Also, 83 (15.63%) patients showed signs of LN involvement, and two patients (0.003%) had distant metastasis.
The results of pathological evaluation of the resected lesions are presented in Table 3.The most frequently observed pathology was PTC in 239 (45%) of the cases, followed by MNG at 31.1%, Hashimoto's thyroiditis at 4.6%, and the follicular variant of PTC with capsular vascular invasion at 4.3%.The malignant group primarily comprised differentiated thyroid cancer, with ATC observed in only 5 cases (1%) within the undifferentiated subgroup.FTC and Hürthle cell carcinoma were identified in 6 (1.2%) and 4 (0.8%) cases, respectively, while MTC constituted 6 cases (1.1%).In the nonmalignant group, follicular lesions, including MNG at 31.1%, Hashimoto's thyroiditis at 4.6%, and colloid goiters at 3.6%, constituted the primary findings.
Other nonmalignant findings, such as lymphocytic thyroiditis (2.3%) and Graves' disease (1.1%) were observed in a smaller number of cases.
T A B L E 1 Demographic and clinical features of thyroidectomy patients in southern Iran.and carry a higher risk of manifesting as a more severe histological phenotype. 26Moreover, a study evaluating the demographic characteristics of thyroid cancer over the last two decades found the highest rate of increase in this type of cancer to be in the age range of 30−50, with PTC exhibiting the highest rate of increase, followed by FTC. 27Considering that the onset age of thyroid cancer is trending younger in recent decades, 28 early preventive and diagnostic methods, including screening, are suggested for the population in the age group at higher risk.
The majority of patients in our study were female (83.5%).The higher incidence of benign thyroid disease in women is often thought to lead to more frequent thyroid investigations and surgeries.
However, in a study by Machens et al., 29 which primarily featured gross thyroid tumors, there wasn't a significant difference in the prevalence of sporadic thyroid microcarcinomas between men and women.This suggests that differential screening may not be a major factor in the observed gender disparities in sporadic thyroid cancers.
Another potential explanation could be gender-specific behavioral differences, with men tending to seek medical attention later than women.Due to the retrospective nature of our study and a high referral rate, no direct data on patients' delay were available.If gender-specific delay was a significant factor, it might have contributed to the generally larger overall tumor size, particularly in FTC. 30 The higher prevalence of Graves' disease among women could also be a contributing factor to the observed sex differences in our study. 31Several factors may contribute to these sex differences, including the higher incidence of thyroid carcinoma and LN metastasis in men, necessitating more intricate or extensive surgeries. 32,33Studies also propose that men may have tougher neck tissues and stronger neck muscles, leading to the potential slipping of ligatures or reopening of previously tied vessels, thereby increasing the risk of hematoma. 33,34Additionally, men are more prone to conditions such as hypertension and engage in unfavorable habits like smoking and drinking. 34However, these factors were not extensively evaluated in our study.Another aspect to consider is the documented higher susceptibility of male patients to postoperative neck hematoma following total thyroidectomy. 35,36Neck hematoma is recognized as the primary cause for reintervention post-thyroidectomy. 37rther exploration is needed to determine if anatomical distinctions could account for this observation. 37Despite potential variations in disease rates between genders, this does not necessarily imply distinct sex-specific rates of malignant progression to thyroid cancer, as our results also demonstrated no significant difference in the incidence of malignancy between male and female gender.
Although we did not examine the socioeconomic status of the patients in our study, previous research has emphasized the persistent challenges of socioeconomic disparities in healthcare access and health beliefs.Individuals with underinsured or uninsured status tend to bear a greater burden of benign thyroid diseases during thyroidectomy, as evidenced by larger pathologic thyroid volumes. 38 our study, the most common presentation of thyroid cancer was thyromegaly.In the malignant group, mass lesions were found to be the predominant clinical manifestation; however, the development of this symptom was not significantly associated with the incidence of thyroid cancer.While only 10% of thyroid nodules are larger than average, these lesions could potentially become clinically significant tumors. 15,39In our case, lesions greater than 5 cm in the largest size were observed in 18 (5.6%)patients, of which 61.1% were classified as nonmalignant.In contrast, of the 114 patients who had lesions smaller than 1 cm, 90.4% were revealed to have malignant tumors.
While these findings suggest that larger thyroid lesions, whether cancerous or noncancerous, are negatively associated with malignant tumors, several studies find size to have no significant relationship with tumor malignancy, [40][41][42] and others associate the increase in tumor size with higher chances of malignancy. 43,44Thus, thyromegaly alone, without considering the pathological aspect of existing lesions, can be misleading in terms of distinguishing between low-and high-risk patients.
To date, available data regarding the clinical significance and prognostic role of LVI remain controversial.In a study by Sezer et al., which evaluated over 600 patients with PTC, the authors reported a correlation between LVI and several factors, including age, sex, tumor size, metastatic LNs, extrathyroidal extension, perineural invasion, and capsular invasion, considering LVI as a marker of aggressive thyroid cancer. 45Associations between LVI and LN metastasis, as well as distant metastasis, have also been reported. 46,47Major vascular invasion is considered to have a significant impact on the survival of patients with thyroid cancer by potentially differentiating between benign and malignant tumors. 48In a study of 45,415   patients with PTC by Pontius et al., compromised survival was observed in patients with LVI compared to those without LVI, suggesting a higher risk of mortality in patients with PTC undergoing thyroidectomy. 47However, our study did not show any significant correlation between LVI and tumor malignancy.
Regional LN metastasis is a variable that reflects the extent of a tumor.Over the years, the prognostic value of LN ratio has been studied, indicating its significant role in predicting the recurrence of PTC 49 and determining the outcome of patients with MTC. 50While an optimal cut-off value of 0.50 has been suggested for patients with PTC undergoing total LN dissection, 51 56 Therefore, it is recommended that more regional studies be performed to determine possible risk factors for less common subtypes of thyroid cancer.
On a similar note, the rise in thyroid cancer incidence can be largely attributed to overdiagnosis.This issue is evident in a study in South Korea, where a 35% reduction in cases of thyroidectomy was observed after a high-profile media appeal recommended against thyroid screening with ultrasound. 57In this regard, in 2017, the United States Preventive Services Taskforce recommended against thyroid cancer screening in asymptomatic patients, emphasizing that screening in this population has no net benefit or might even induce more harm than good. 58An instance of potential harm can be seen in the high percentage of total thyroidectomies in patients with thyroid cancer (85% in a study by L. Davies, as well as 92.1% in our study), which can put patients at risk of postoperative complications. 2 Considering that the limited variations of thyroid cancer that can cause mortality almost always present with symptoms, even if these subtypes are detected by screening, the course of their outcomes is unlikely to be affected. 59,60 our study, a total of 478 (93.0) total thyroidectomies and 23 (4.5) subtotal thyroidectomies were performed, which with the 2015 ATA guidelines. 175][66][67][68][69][70] Approximately one-third of thyroid cancer patients present with regional nodal disease, 71,72 and the clinical approach to LN dissection may vary based on the underlying pathology. 73In our study, total thyroidectomy along with CLND was performed in 29.8% of the patients, 70.4% of whom were associated with a malignant thyroid lesion.Several studies have also highlighted potential complications of CLND, including hypoparathyroidism, damage to the superior branch of the recurrent laryngeal nerve, and damage to the trachea or esophagus. 74,75These complications seem to increase when central neck dissection is performed after total thyroidectomy. 76Regarding the thymus, limited cases in our study underwent thymectomy, with no significant correlation found with malignant tumor occurrence.Studies have stated that routine thymectomy offers minimal oncologic benefit and poses a high risk of postoperative hypocalcemia.However, the study has limitations.The lack of a long follow-up period and the absence of an analysis of socioeconomic and racial factors are notable limitations.Since the study is based on thyroid cancer patients who underwent thyroidectomy, not all existing cases of thyroid cancer were included, and the amount of missing data, along with the lack of information regarding long-term follow-up, adds to the study's limitations.

| CONCLUSIONS
this retrospective cross-sectional study, we evaluated the medical records of patients admitted to Namazi and Bu-ali Hospitals in Fars province from 2015 to 2020.These hospitals serve as referral centers for thyroid surgery in Southern Iran.We included patients with postoperative sample pathological reports and excluded any files related to pathologies unrelated to the thyroid.Two qualified general practitioners carefully reviewed the files by referring to the hospital archives and categorizing them according to specific disease codes.From these patient records, information pertaining to thyroid cancer disease, including baseline demographic, clinical, operative, and pathologic features was extracted.Demographic data included age (categorized into groups of ≤18, 19-25, 26-35, 36-45, 46-55, >55) and gender.Clinical features included signs and symptoms on admission, as well as a history of previous subtotal thyroidectomy.Surgical features comprised information on thyroidectomy, LN dissection, thymectomy, the number of isolated and involved nodes (categorized as none, 1−10, 11−20, >20, and none, 1-3, >3, respectively), size, area, and volume of the tumoral lesion (categorized as ≤1, 1-3, 3.01-5, >5 cm for size, ≤1, 1-10, >10 cm 2 for area, and ≤1, 1−10, >10 cm 3 for volume), TNM classification, 23 location of the lesion, focality, capsule involvement, mitosis, extrathyroidal invasion, lymphovascular invasion (LVI), perineural invasion, encapsulation, calcification, marginal involvement, and necrosis.The pathology features were assessed based on postoperation permanent pathology samples.The data were inputted into SPSS version 26.0 software and subsequently analyzed.Descriptive statistics are presented as frequency and percentage (%).The distribution of continuous variables was assessed using the Shapiro−Wilk test.For normally distributed variables, the results are reported as mean and standard deviation (SD), while for non-normally distributed variables, the values are reported as median and the first and third quantiles [Q1-Q3].The association between thyroid cancer features and related factors is examined using specific χ 2 tests or Fisher's exact test for categorical variables, and the independent sample t-test or Mann−Whitney test for continuous variables.A p-value less than 0.05 is considered statistically significant.
Clinical and surgical features of patients who underwent thyroidectomy.Histopathological findings from thyroidectomy patients in Southern Iran.
25te: Bold values indicate a significant association. a χ 2 /Fisher's exact test or independent sample t-test.T A B L E 2 location, with PTCs being the predominant histopathological finding.Notably, this study represents the first population-level investigation examining the impact of patient demographics and clinical and pathological factors on thyroidectomy in patients with thyroid lesions in Iran.Our findings indicate that age, thyromegaly, method of thyroidectomy and LN dissection, size, and location of thyroid lesions were correlated with tumor malignancy.As the incidence of thyroid association of age with the risk of malignancy in 1022 patients undergoing consecutive thyroidectomy, rates of DTC did not differ between patients aged <45 or ≥45, and it occurred more frequently in patients younger than 50 years.25Kwongetal.also found that with increasing age, the risk of thyroid nodules being malignant decreases.However, clinically relevant nodules are more prevalent in older age T A B L E 2 (Continued) Note: Bold values indicate a significant association. a χ 2 /Fisher's exact test or Mann−Whitney U t-test.T A B L E 3Abbreviations: FLUS, follicular lesion of undetermined significance; FTC, follicular thyroid cancer; MNG, multinodular goiter; MTC, medullary thyroid carcinoma; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC, papillary thyroid cancer.
Overall, evidence suggests limited oncologic benefits and increased risks associated with thymectomy during CLND.Nonetheless, specialized randomized studies and long-term follow-ups are highly necessary to provide precise answers regarding the prophylactic and therapeutic to what extent of surgical resection can be beneficial for patients undergoing thyroidectomy.Ultimately, while PTC has been the most common histopathological finding in thyroid cancer studies, the focus on this entity has limited the exploration of other less-common types of thyroid cancer and their association with demographic and tumor clinical characteristics.This study addresses this gap, leveraging advanced diagnostic tools, updated medical diagnostic methods, and expert physicians as strengths.Additionally, the study provides a valuable overview of various types of both malignant and nonmalignant thyroid cancers in correlation with demographic and clinical findings.It is recommended that more detailed studies be conducted to evaluate risk factors, tumor characteristics, treatment options, and the survival and mortality risks of different types of thyroid tumors, considering the significant findings presented here.
79,77Li et al.advocated for thymus preservation, citing its benefits in safeguarding parathyroid glands and preventing transient hypoparathyroidism.78Nasiri et alreported a higher incidence of hypocalcemia in PTC patients undergoing CLND with thymectomy, recommending against this procedure.79 Our findings indicate an annual rate of 88.8 thyroidectomies in Southern Iran, with a predominant prevalence of PTC.Key associations with tumor malignancy include age, thyromegaly, total thyroidectomy, and LN dissection.Demographic trends reveal that higher age is linked to a lower rate of malignant tumors, consistent with existing literature.Our study offers crucial insights into the thyroid cancer status in Southern Iran, highlighting the need for further research to explore risk factors, treatment outcomes, and long-term prognosis for various thyroid tumor types, and studies consisting of all operated and non-operated patients with thyroid cancers.